Glenn Murray put Crystal Palace ahead with a tap-in from close range before Jason Puncheon fired in a brilliant free-kick from the edge of the box.
Yaya Toure's fierce strike pulled a goal back for fourth-placed City but Palace held on to move up to 11th.
City are nine points behind Chelsea and also below Arsenal and Manchester United, who they play on Sunday.
And Manuel Pellegrini's side, who have played a game more than Chelsea, have now lost their past four away matches.
Having slipped to fourth after victories for Arsenal and derby rivals United on Saturday, City were under pressure to come up with a win of their own.
But they were almost caught cold inside 60 seconds when Martin Kelly picked out Wilfried Zaha with a low cross, but the winger blasted over.
City, who had not won in their four previous visits to London, responded well, dominating possession and pinning Palace back to the edge of their own box.
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